Expression and localization of the progesterone receptor in mouse and human reproductive organs

Abstract

The effects of gonadotropins on progesterone receptor (PR) expression and localization in the mouse oviduct, uterus, and ovary was examined. In the oviduct ciliated epithelial cells of adult mice and human revealed a unique PR localization to the lower half of the motile cilia whereas the nuclei were unstained or faintly stained. Pubertal female mice were further studied by confocal laser scanning microscopy and western blotting before and after injection with FSH and LH followed by human chorionic gonadotropin (hCG) injection after a 48-h period. PR immunolocalization to the oviduct cilia was greatly increased in pubertal mice upon hCG stimulation. In neighboring goblet cells, the PR staining was confined to the nuclei. Nuclear PR localization was evident in epithelial cells of the uterus as well as in a fraction of stromal and muscle cells. Staining intensity and number of stained cells was not affected by hormone stimulation. In the ovary, weak PR immunolocalization was observed in unprimed animals but increased significantly after hCG stimulation. In granulosa cells of preovulatory follicles PR was exclusively observed in mural cells, whereas cumulus cells remained negative. At all stages examined, primary granulosa cell cilia lacked PR staining. SDS-PAGE and western blotting analysis of tissues from oviduct, uterus, and ovary confirmed antibody specificity, and identified two bands corresponding to the PR isoforms PR-A and PR-B. Upon hCG stimulation, a new band cross-reacting with anti-PR emerged above the PR-A form in oviduct fractions, suggesting LH-induced phosphorylation of PR-A. We suggest that ciliary PR in the oviduct plays a role in progesterone signaling after ovulation, possibly via non-genomic events. These novel findings warrant further studies of oviduct and postovulatory signaling events and suggest a sensory role for oviduct cilia in the process of oocyte transport/fertilization.

New evidence for the involvement of prostaglandin receptor EP4b in ovulation of the medaka, Oryzias latipes

“…The role of PGR in ovulation has been extensively studied in mammals (Natraj and Richards, 1993;Gava et al, 2004;Teilmann et al, 2006). In addition, a handful of studies on the function of Pgr in teleosts have also been published Thomas, 1995, 1999;Toda et al, 2000;Chen et al, 2010;Hanna et al, 2010).…”

Oviduct: roles in fertilization and early embryo development

“…P 4 reduces CBF through classical progesterone receptors (PGRs) expressed on the ciliated epithelial cells in a dosage-dependent manner in humans and mice (Mahmood et al 1998, Bylander et al 2010, 2013. A non-classical PGR is expressed in the lower part of the cilia stalk in mouse oviducts (Teilmann et al 2006). Recent studies in mice indicated that low dosage of P 4 and short activation time (within 30 min) are sufficient to reduce oviductal CBF (Bylander et al 2010(Bylander et al , 2013.…”

Sensory reception is an attribute of both primary cilia and motile cilia

“…The membranes of motile cilia of the mammalian oviduct contain progesterone receptors [mouse and human (Teilmann et al, 2006;Nutu et al, 2009)], estrogen receptor- [rat (Shao et al, 2007)] and interleukin-6 receptor (IL6R) [mouse and human (Shao et al, 2009)]. Furthermore, progesterone (Mahmood et al, 1998;Paltieli et al, 2000;Wessel et al, 2004) and interleukin-6 (Papathanasiou et al, 2008) regulate oviductal ciliary beat frequency.…”